1. A plasmid cDNA library was constructed using poly(A+)RNA isolated from the livers of rats treated with triiodothyronine and fed a high carbohydrate diet. The library was screened by differential colony hybridization and dot blot hybridization using 32P-cDNA probes made from hypothyroid and hyperthyroid rat liver poly(A+)RNA. cDNAs for 8 different T3 responsive mRNAs were obtained. Then they were used to determine: a) relative mRNA level in different thyroid states and response to a high carbohydrate diet; b) kinetic response to receptor saturating doses of triiodothyronine in hypothyroid animals. Several of these cDNA clones may serve as models for the study of the mechanism of action of T3 on the regulation of gene expression. 2. We have demonstrated by hybridization assays with malic enzyme cDNA that: a) liver malic enzyme synthesis is directed by two distinct and functional cytoplasmic mRNAs; b) malic enzyme activity is modulated at the pretranslational level by thyroid hormones and carbohydrate diet, presumably through regulation of the rate of malic enzyme gene transcription; c) the level of expression of malic enzyme gene as well as its regulation by T3 are tissue specific and the hormonal stimulation affects both malic enzyme mRNAs to a similar degree in the T3 responsive tissues (liver, heart and kidney). 3. Preliminary results show that T3 regulates the rate of transcription of specific genes to some extent.